A gene atlas of the mouse and human protein-encoding transcriptomes

Su, Andrew I.; Wiltshire, Tim; Batalov, Serge; Lapp, Hilmar; Ching, Keith A.; Block, David E.; Zhang, Jie; Soden, Richard; Hayakawa, Mimi; Kreiman, Gabriel; Cooke, M.; Walker, John R.; Hogenesch, John B.

doi:10.1073/pnas.0400782101

Cited by 3,129 publications

(3,483 citation statements)

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“…To identify previously uncharacterized cell-surface-associated proteins, we applied a ranking strategy to all 555 orthologues and prioritized proteins with no previous links to cardiac function on the basis of phenotype ontology (http://www.informatics.jax. org) and cardiac enrichment on the basis of threefold upregulation in cardiac tissue, using publicly available microarrays 13 . This approach identified Tmem65 as our top candidate (Fig.…”

Section: Resultsmentioning

confidence: 99%

Evolutionarily conserved intercalated disc protein Tmem65 regulates cardiac conduction and connexin 43 function

et al. 2015

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Membrane proteins are crucial to heart function and development. Here we combine cationic silica-bead coating with shotgun proteomics to enrich for and identify plasma membrane-associated proteins from primary mouse neonatal and human fetal ventricular cardiomyocytes. We identify Tmem65 as a cardiac-enriched, intercalated disc protein that increases during development in both mouse and human hearts. Functional analysis of Tmem65 both in vitro using lentiviral shRNA-mediated knockdown in mouse cardiomyocytes and in vivo using morpholino-based knockdown in zebrafish show marked alterations in gap junction function and cardiac morphology. Molecular analyses suggest that Tmem65 interaction with connexin 43 (Cx43) is required for correct localization of Cx43 to the intercalated disc, since Tmem65 deletion results in marked internalization of Cx43, a shorter half-life through increased degradation, and loss of Cx43 function. Our data demonstrate that the membrane protein Tmem65 is an intercalated disc protein that interacts with and functionally regulates ventricular Cx43.

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Section: Resultsmentioning

confidence: 99%

Evolutionarily conserved intercalated disc protein Tmem65 regulates cardiac conduction and connexin 43 function

et al. 2015

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“…Among different human tissues, the maximum gene expression was found in the liver and peripheral blood leukocytes [6,22]. A large-scale analysis of the human transcriptome indicated that the PBEF gene is highly expressed in whole blood, over 100 times of the median abundance, while the expression in adipocytes is just about 2 times of the median abundance (GEO series GSE1133) [23].…”

Section: Discussionmentioning

confidence: 99%

The circulating PBEF/NAMPT/visfatin level is associated with a beneficial blood lipid profile

Wang

Greevenbroek

Bouwman

et al. 2007

Pflugers Arch - Eur J Physiol

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Visfatin with the official gene name pre-B cell colony-enhancing factor 1 (PBEF) and the protein name nicotinamide phosphoribosyltransferase (NAMPT) is a recently discovered adipocyte-secreted protein that was shown by some to be associated with visceral fat and insulin resistance. To explore the link between PBEF/ NAMPT/visfatin and lipid metabolism, we analyzed the relation of its plasma level with several parameters of adiposity, insulin resistance and the circulating blood lipid profile in a group of general population (n=40) and a group of subjects who are genetically predisposed to insulin resistance and hyperlipidemia (n=35). In both groups and pooled cohort, PBEF/NAMPT/visfatin lacked association with whole body adiposity, but correlated positively with HDL-cholesterol and negatively with triglycerides. The data suggested a negative correlation of the PBEF level with visceral fat and insulin resistance. But this negative correlation completely disappeared after adjustment for lipid profile. We concluded that circulating PBEF/NAMPT/ visfatin level is an indicator of beneficial lipid profile in non-diabetic Caucasian subjects. The relation to lipid metabolism does not depend on visceral obesity and insulin resistance, but may be linked to its enzymatic function in NAD metabolism.

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“…Other HSPG genes, including syndecan-2, -3 and -4 and the six glypican genes, were not expressed ('absent' call) by most myeloma cell samples, and displayed a very weak signal compared to syndecan-1. This lack of expression cannot be attributed to a failed detection by a non-functional Affymetrix probeset, as a high expression of the 10 HSPG genes could be detected on various normal tissues according to the data available (Su et al, 2004) (data not shown). A further HSPG, the variant v3 of CD44, was very weakly expressed on HMCLs (MFI ranging from 5-15, data not shown), in agreement with previous reports (Derksen et al, 2002;Van Driel et al, 2002).…”

Section: Only Hs-binding Egf-family Members Have a Myeloma Cell Growtmentioning

confidence: 98%

Heparan sulphate proteoglycans are essential for the myeloma cell growth activity of EGF-family ligands in multiple myeloma

et al. 2006

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The epidermal growth factor (EGF)/EGF-receptor (ErbB1-4) family is involved in the biology of multiple myeloma (MM). In particular, ErbB-specific inhibitors induce strong apoptosis of myeloma cells (MMC) in vitro.To delineate the contribution of the 10 EGF-family ligands to the pathogenesis of MM, we have assessed their expression and biological activity. Comparing Affymetrix DNA-microarray-expression-profiles of CD138-purified plasma-cells from 65 MM-patients and 7 normal individuals to those of plasmablasts and B-cells, we found 5/10 EGF-family genes to be expressed in MMC. Neuregulin-2 and neuregulin-3 were expressed by MMC only, while neuregulin-1, amphiregulin and transforming growth factor-a were expressed by both MMC and normal plasma-cells. Using real-time polymerase chain reaction, we found HB-EGF, amphiregulin, neuregulin-1 and epiregulin to be expressed by cells from the bone marrow-environment. Only the EGF-members able to bind heparan-sulphate proteoglycans (HSPGs) -neuregulin-1, amphiregulin, HB-EGF -promote the growth of MMC. Those ligands strongly bind MMC through HSPGs. The binding and the MMC growth activity was abrogated by heparitinase, heparin or deletion of the HS-binding domain. The number of HS-binding EGF ligand molecules bound to MMC was higher than 10 5 molecules/cell and paralleled that of syndecan-1. Syndecan-1, the main HSPG present on MM cells, likely concentrates high levels of HS-binding-EGF-ligands at the cell membrane and facilitates ErbB-activation. Altogether, our data further identify EGF-signalling as promising target for MM-therapy.

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A gene atlas of the mouse and human protein-encoding transcriptomes

Cited by 3,129 publications

References 37 publications

Evolutionarily conserved intercalated disc protein Tmem65 regulates cardiac conduction and connexin 43 function

Evolutionarily conserved intercalated disc protein Tmem65 regulates cardiac conduction and connexin 43 function

The circulating PBEF/NAMPT/visfatin level is associated with a beneficial blood lipid profile

Heparan sulphate proteoglycans are essential for the myeloma cell growth activity of EGF-family ligands in multiple myeloma

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